Sumatriptan Succinate

Sagent Pharmaceuticals

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use sumatriptan succinate safely and effectively. See full prescribing information for sumatriptan succinate. Sumatriptan Injection, USP, for subcutaneous useInitial U.S. Approval: 1992 INDICATIONS AND USAGESumatriptan Injection, USP is a serotonin (5-HT1B/1D) receptor agonist (triptan) indicated for: Acute treatment of migraine with or without aura in adults (1) Acute treatment of cluster headache in adults (1) Limitations of Use: Use only if a clear diagnosis of migraine or cluster headache has been established. (1) Not indicated for the prevention of migraine attacks. (1) DOSAGE AND ADMINISTRATION For subcutaneous use only. (2.1) Acute treatment of migraine: 1- to 6-mg Single dose. (2.1) Acute treatment of cluster headache: 6-mg Single dose. (2.1) Maximum dose in a 24-hour period: 12 mg, Separate doses by at least 1 hour. (2.1) Patients receiving doses other than 6 mg: Use the 6-mg single-dose vial. (2.3) DOSAGE FORMS AND STRENGTHS Injection: 6-mg single-dose vial (3) CONTRAINDICATIONS Coronary artery disease or coronary vasospasm (4) Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders (4) History of stroke, transient ischemic attack, or hemiplegic or basilar migraine (4) Peripheral vascular disease (4) Ischemic bowel disease (4) Uncontrolled hypertension (4) Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another triptan) or of an ergotamine-containing medication (4) Current or recent (past 2 weeks) use of monoamine oxidase-A inhibitor (4) Known hypersensitivity to sumatriptan (4) Severe hepatic impairment (4) WARNINGS AND PRECAUTIONS Myocardial ischemia/infarction and Prinzmetal's angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. (5.1) Arrhythmias: Discontinue sumatriptan succinate if occurs. (5.2) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for coronary artery disease in patients at high risk. (5.3) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue sumatriptan succinate if occurs. (5.4) Gastrointestinal ischemia and infarction events, peripheral vasospastic reactions: Discontinue sumatriptan succinate if occurs. (5.5) Medication overuse headache: Detoxification may be necessary. (5.6) Serotonin syndrome: Discontinue sumatriptan succinate if occurs. (5.7) Increase in blood pressure: Monitor blood pressure. (5.8) Anaphylactic/anaphylactoid reactions: Discontinue sumatriptan succinate if occurs (5.9) Seizures: Use with caution in patients with epilepsy or a lowered seizure threshold. (5.10) Side EffectsMost common adverse reactions (≥5% and > placebo) were injection site reactions, tingling, dizziness/vertigo, warm/hot sensation, burning sensation, feeling of heaviness, pressure sensation, flushing, feeling of tightness, and numbness (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm (8.1) Geriatric use: A cardiovascular evaluation is recommended in those who have other cardiovascular risk factors prior to receiving sumatriptan succinate. (8.5)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 SUMATRIPTAN SUCCINATE INDICATIONS AND USAGE
• 2 SUMATRIPTAN SUCCINATE DOSAGE AND ADMINISTRATION
  • 2.1 Dosing Information
  • 2.3 Administration of Doses of Sumatriptan Succinate Other Than 6 mg
• 3 DOSAGE FORMS AND STRENGTHS
• 4 SUMATRIPTAN SUCCINATE CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina
  • 5.2 Arrhythmias
  • 5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure
  • 5.4 Cerebrovascular Events
  • 5.5 Other Vasospasm Reactions
  • 5.6 Medication Overuse Headache
  • 5.7 Serotonin Syndrome
  • 5.8 Increase in Blood Pressure
  • 5.9 Anaphylactic/Anaphylactoid Reactions
  • 5.10 Seizures
• 6 SUMATRIPTAN SUCCINATE ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Postmarketing Experience
• 7 DRUG INTERACTIONS
  • 7.1 Ergot-Containing Drugs
  • 7.2 Monoamine Oxidase-A Inhibitors
  • 7.3 Other 5-HT Agonists
  • 7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 10 OVERDOSAGE
• 11 SUMATRIPTAN SUCCINATE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
  • 13.2 Animal Toxicology and/or Pharmacology
• 14 CLINICAL STUDIES
  • 14.1 Migraine
  • 14.2 Cluster Headache
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events
  • 17.2 Anaphylactic/Anaphylactoid Reactions
  • 17.3 Medication Overuse Headache
  • 17.4 Pregnancy
  • 17.5 Nursing Mothers
  • 17.6 Ability To Perform Complex Tasks
  • 17.7 Serotonin Syndrome
  • 17.8 How to Use Sumatriptan Injection, USP

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Sumatriptan Injection, USP is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache.

Limitations of Use:

• Use only if a clear diagnosis of migraine or cluster headache has been established.
• If a patient has no response to the first migraine attack treated with Sumatriptan Injection, USP, reconsider the diagnosis of migraine before Sumatriptan Injection, USP is administered to treat any subsequent attacks.
• Sumatriptan Injection, USP is not indicated for the prevention of migraine attacks.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information

The maximum single recommended adult dose of sumatriptan injection for the acute treatment of migraine or cluster headache is 6 mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, lower doses (1 to 5 mg) may be used [see Clinical Studies (14.1)]. For the treatment of cluster headache, the efficacy of lower doses has not been established.

The maximum cumulative dose that may be given in 24 hours is 12 mg, two 6-mg injections separated by at least 1 hour. A second 6-mg dose should only be considered if some response to a first injection was observed.

2.3 Administration of Doses of Sumatriptan Succinate Other Than 6 mg

In patients receiving doses other than 6 mg, use the 6-mg single-dose vial. Visually inspect the vial for particulate matter and discoloration before administration. Do not use if particulates and discolorations are noted.

3 DOSAGE FORMS AND STRENGTHS

• Injection: 6-mg single-dose vial

4 CONTRAINDICATIONS

Sumatriptan injection is contraindicated in patients with:

• Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina [see Warnings and Precautions (5.1)].
• Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)].
• History of stroke or transient ischemic attack (TIA) because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)].
• History of hemiplegic or basilar migraine.
• Peripheral vascular disease [see Warnings and Precautions (5.5)].
• Ischemic bowel disease [see Warnings and Precautions (5.5)].
• Uncontrolled hypertension [see Warnings and Precautions (5.8)].
• Recent (i.e., within 24 hours) use of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine₁ (5-HT₁) agonist [see Drug Interactions (7.1, 7.3)].
• Concurrent administration of an MAO-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].
• Known hypersensitivity to sumatriptan [see Warnings and Precautions (5.9) and Adverse Reactions (6.2)].
• Severe hepatic impairment [see Clinical Pharmacology (12.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina

The use of sumatriptan injection is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of sumatriptan injection. Some of these reactions occurred in patients without known CAD. 5-HT₁ agonists, including sumatriptan injection, may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD.

Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection. If there is evidence of CAD or coronary artery vasospasm, sumatriptan injection is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of sumatriptan injection in a medically supervised setting and performing an electrocardiogram (ECG) immediately following sumatriptan injection. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of sumatriptan injection.

Evaluate patients with signs or symptoms suggestive of angina following sumatriptan injection for the presence of CAD or Prinzmetal's angina before receiving additional doses of sumatriptan injection.

5.2 Arrhythmias

Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT₁ agonists. Discontinue sumatriptan injection if these disturbances occur. Sumatriptan injection is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure

As with other 5-HT₁ agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan injection and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of sumatriptan injection is contraindicated in patients shown to have CAD and those with Prinzmetal's variant angina.

5.4 Cerebrovascular Events

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT₁ agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT₁ agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue sumatriptan injection if a cerebrovascular event occurs.

As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, exclude other potentially serious neurological conditions. Sumatriptan injection is contraindicated in patients with a history of stroke or TIA.

5.5 Other Vasospasm Reactions

5-HT₁ agonists, including sumatriptan injection, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. Until further evaluation, sumatriptan injection is contraindicated in patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT₁ agonist.

Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT₁ agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT₁ agonists have not been clearly established.

5.6 Medication Overuse Headache

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, combination of drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches, or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

5.7 Serotonin Syndrome

Serotonin syndrome may occur with triptans, including sumatriptan injection, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.4)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue sumatriptan injection if serotonin syndrome is suspected.

5.8 Increase in Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT₁ agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with sumatriptan succinate. Sumatriptan injection is contraindicated in patients with uncontrolled hypertension.

5.9 Anaphylactic/Anaphylactoid Reactions

Anaphylactic/anaphylactoid reactions have occurred in patients receiving sumatriptan. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. Sumatriptan injection is contraindicated in patients with prior serious anaphylactic reaction.

5.10 Seizures

Seizures have been reported following administration of sumatriptan. Some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures. There are also reports in patients where no such predisposing factors are apparent. Sumatriptan injection should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the labeling:

• Myocardial ischemia, myocardial infarction, and Prinzmetal's angina [see Warnings and Precautions (5.1)]
• Arrhythmias [see Warnings and Precautions (5.2)]
• Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3)]
• Cerebrovascular events [see Warnings and Precautions (5.4)]
• Other vasospasm reactions [see Warnings and Precautions (5.5)]
• Medication overuse headache [see Warnings and Precautions (5.6)]
• Serotonin syndrome [see Warnings and Precautions (5.7)]
• Increase in blood pressure [see Warnings and Precautions (5.8)]
• Anaphylactic/anaphylactoid reactions [see Warnings and Precautions (5.9)]
• Seizures [see Warnings and Precautions (5.10)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Migraine Headache: Table 1 lists adverse reactions that occurred in 2 US placebo-controlled clinical trials in migraine subjects [Studies 2 and 3, see Clinical Studies (14.1)] following either a single 6-mg dose of sumatriptan injection or placebo. Only reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection 6 mg and that occurred at a frequency greater than the placebo group are included in Table 1.

The incidence of adverse reactions in controlled clinical trials was not affected by gender or age of the subjects. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

Cluster Headache: In the controlled clinical trials assessing the efficacy of sumatriptan injection as a treatment for cluster headache [Studies 4 and 5, see Clinical Studies (14.2)], no new significant adverse reactions were detected that had not already been identified in trials of sumatriptan succinate in subjects with migraine.

Overall, the frequency of adverse reactions reported in the trials of cluster headache was generally lower than in the migraine trials. Exceptions include reports of paresthesia (5% sumatriptan succinate, 0% placebo), nausea and vomiting (4% sumatriptan succinate, 0% placebo), and bronchospasm (1% sumatriptan succinate, 0% placebo).

Other Adverse Reactions: In the paragraphs that follow, the frequencies of less commonly reported adverse reactions are presented. Reaction frequencies were calculated as the number of subjects reporting a reaction divided by the total number of subjects (N = 6,218) exposed to subcutaneous sumatriptan injection. All reported reactions are included except those already listed in the previous table. Reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent are defined as those occurring in at least 1/100 subjects, infrequent are those occurring in 1/100 to 1/1,000 subjects, and rare are those occurring in fewer than 1/1,000 subjects.

•   Cardiovascular: Infrequent were hypertension, hypotension, bradycardia, tachycardia, palpitations, and syncope. Rare was arrhythmia.
•   Gastrointestinal: Frequent was abdominal discomfort.
•   Musculoskeletal: Frequent were muscle cramps.
•   Neurological: Frequent was anxiety. Infrequent were mental confusion, euphoria, agitation, tremor. Rare were myoclonia, sleep disturbance, and dystonia.
•   Respiratory: Infrequent was dyspnea.
•   Skin: Infrequent were erythema, pruritus, and skin rashes.
•   Miscellaneous: Infrequent was “serotonin agonist effect”.

Adverse Events Observed With Other Formulations of Sumatriptan Succinate: The following adverse events occurred in clinical trials with sumatriptan tablets and sumatriptan nasal spray. Because the reports include events observed in open and uncontrolled trials, the role of sumatriptan succinate in their causation cannot be reliably determined. All reported events are included except those already listed, those too general to be informative, and those not reasonably associated with the use of the drug.

•   Cardiovascular: Angina, cerebrovascular lesion, heart block, peripheral cyanosis, phlebitis, thrombosis.
•   Gastrointestinal: Abdominal distention and colitis.
•   Neurological: Convulsions, hallucinations, syncope, suicide, and twitching.
•   Miscellaneous: Edema, hypersensitivity, swelling of extremities, and swelling of face.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of sumatriptan tablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to sumatriptan succinate or a combination of these factors.

•   Blood: Hemolytic anemia, pancytopenia, thrombocytopenia.
•   Ear, Nose, and Throat: Deafness.
•   Eye: Ischemic optic neuropathy, retinal artery occlusion, retinal vein thrombosis.
•   Neurological: Central nervous system vasculitis, cerebrovascular accident, serotonin syndrome, subarachnoid hemorrhage.
•   Non-Site Specific: Angioedema, cyanosis, temporal arteritis.
•   Skin: Exacerbation of sunburn, hypersensitivity reactions (allergic vasculitis, erythema, pruritus, rash, shortness of breath, urticaria), photosensitivity. Following subcutaneous administration of sumatriptan succinate, pain, redness, stinging, induration, swelling, contusion, subcutaneous bleeding, and, on rare occasions, lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) have been reported.
•   Urogenital: Acute renal failure.

7 DRUG INTERACTIONS

7.1 Ergot-Containing Drugs

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan injection within 24 hours of each other is contraindicated.

7.2 Monoamine Oxidase-A Inhibitors

MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of sumatriptan injection in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].

7.3 Other 5-HT Agonists

Because their vasospastic effects may be additive, coadministration of sumatriptan injection and other 5-HT₁ agonists (e.g., triptans) within 24 hours of each other is contraindicated.

7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome

Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, or SNRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C: There are no adequate and well-controlled trials of sumatriptan injection in pregnant women. Sumatriptan injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

When sumatriptan was administered intravenously to pregnant rabbits daily throughout the period of organogenesis, embryolethality was observed at doses at or close to those producing maternal toxicity. These doses were less than the maximum recommended human dose (MRHD) of 12 mg/day on a mg/m² basis. Oral administration of sumatriptan to rabbits during organogenesis was associated with increased incidences of fetal vascular and skeletal abnormalities. The highest no-effect dose for these effects was 15 mg/kg/day. The intravenous administration of sumatriptan to pregnant rats throughout organogenesis at doses that are approximately 10 times the MRHD on a mg/m² basis, did not produce evidence of embryolethality. The subcutaneous administration of sumatriptan to pregnant rats prior to and throughout pregnancy did not produce evidence of embryolethality or teratogenicity.

8.3 Nursing Mothers

It is not known whether sumatriptan is excreted in human breast milk following subcutaneous administration. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from sumatriptan succinate, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness of sumatriptan injection in pediatric patients under 18 years of age have not been established; therefore, sumatriptan injection is not recommended for use in patients under 18 years of age.

Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 adolescent migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.

Five controlled clinical trials (2 single-attack trials, 3 multiple-attack trials) evaluating oral sumatriptan succinate (25 to 100 mg) in pediatric subjects aged 12 to 17 years enrolled a total of 701 adolescent migraineurs. These trials did not establish the efficacy of oral sumatriptan succinate compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these subjects appeared to be both dose- and age-dependent, with younger subjects reporting reactions more commonly than older adolescents.

Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan succinate. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan succinate; clinical signs occurred within 1 day of drug administration. Since clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan succinate are not presently available, the use of sumatriptan succinate in patients under 18 years of age is not recommended.

8.5 Geriatric Use

Clinical trials of sumatriptan injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection [see Warnings and Precautions (5.1)].

10 OVERDOSAGE

No gross overdoses in clinical practice have been reported. Coronary vasospasm was observed after intravenous administration of sumatriptan injection [see Contraindications (4)]. Overdoses would be expected from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly cause convulsions, tremor, inactivity, erythema of the extremities, reduced respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation, hair loss, and scab formation), and paralysis.

The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with sumatriptan injection should continue for at least 10 hours or while symptoms or signs persist.

It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

11 DESCRIPTION

Sumatriptan Injection, USP contains sumatriptan succinate, a selective 5-HT_1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure: